Breaking Down the Differential Diagnosis for the New NP

Last Updated/Verified: Mar 31, 2024

A differential diagnosis is a list of potential conditions a patient may have. Through my experience as an instructor, I have found that NP students often struggle with this difficult task. However, this is an incredibly important skill to master, as it is a foundation for providing excellent patient care. Adopting a systematic way of thinking can help organize an NP's thoughts.

Differential Diagnosis Challenges:

  • It is impossible to know every symptom for every single disease
  • The process can take a lot of time and research
  • Patients won't always be honest or tell the whole story
  • There is no "one size fits all" approach

Steps to Completing a Differential Diagnosis

Following these steps will help new NPs develop a comprehensive differential diagnosis.

1. Taking a Good History

The first step in conducting a differential diagnosis is completing and reviewing an accurate and thorough evaluation of a patient's medical, surgical, social, and family history. An accurate medication list is important as well. These areas often include details that will be helpful to refer to later on.

2. Physical Exam

A great deal of information about a patient can be discovered without using a stethoscope. Watching posture, breathing, and other behaviors can provide a wealth of information. While a meticulous physical exam is critical, never discount the non-verbal clues displayed by the patient.

3. Diagnostics

A thorough review of a patient's available labs and diagnostic imaging is another important aspect. Tests will often definitively result in a diagnosis, but not always. In these cases, combining diagnostic results with the physical exam findings and patient history will be necessary for the diagnosis. Sometimes, testing will need to be ordered. Beginning to think about potential conditions can help determine which types of tests may lead to a diagnosis.

4. Thinking Process

Compiling a patient's history, physical exam, and diagnostic test findings requires the ability to synthesize the information. This is a skill that will not be learned immediately, but will instead develop over time.

An Experienced NP's Process

Here are the steps I take when developing a differential diagnosis. At this point in my career, I am able to do this in my head without writing it down. However, I would advise new NPs to take notes, as information can be overwhelming when clicking through charts.


Review the patient chart (if available) and chief complaint of the visit before the patient arrives. Here, I can start to develop a potential list of causes for their symptoms. It is important to not let any bias cloud judgment, as keeping an open eye and mind is critical


During the visit, confirm the patient's full and accurate history and perform a physical exam.


Review any previous imaging or laboratory data that may be relevant to the patient's current presentation.


Ask the patient many questions and most importantly, listen to their answers! Using the OLDCARTS system works best for me (Onset, Location, Duration, Character, Aggravating factors, Relieving factors, Timing, and Severity).


During the above steps, I will be going through a list of possible causes based on experiences with past patients. I also draw on what I have learned or read previously over the years. The main question I keep asking is "what could this be?"

System-based thinking is a helpful way to organize my thoughts. For example, if shortness of breath is a presenting symptom, I would think of all potential causes and compare them with the patient's exam findings and history to arrive at a list of differentials. Once I have a few differential diagnoses, I will review them, determine what fits best at the moment, and treat them appropriately. I include a list of the differentials in my documentation for easy reference by myself or another provider who may see the patient in the future.

Keep in mind that common diagnoses are frequent, and not every patient will have a rare illness that nobody has ever seen before. It does happen occasionally though!

Follow Up

Shortly after providing a diagnosis, I follow up with the patient to make sure there has been a resolution of their symptoms. If not, I begin looking into other causes.


If I don't know the answer or am unsure of what to do, I collaborate with another provider and ask questions. It is absolutely OK to not have all of the answers, and transparency with the patient is important. Letting a patient know that I don't have the answer but will do my best to find it will help put them at ease.


The process reviewed above is just one way to develop a differential diagnosis. As the new NP settles into practice, they will determine what works best for them. While obtaining a differential diagnosis is a critical skill for NPs, it will take time to fully master. Therefore, never hesitate to ask for support or collaborate with another provider. With enough time and experience, this will become much easier to accomplish.

Julie Scott
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