Establishing a differential diagnosis can be challenging even for expert advanced practice nurses (APRNs), let alone students. This easy-access clinical guide to commonly seen symptoms, written for APRN students and new practitioners, describes step by step how to obtain a reliable patient history and choose the appropriate directed physical exam for the presenting problem, followed by how to use this patient history and physical exam findings to form a differential diagnosis. Unfolding case scenarios provided for each symptom further demonstrate a sound process for formulating a differential diagnosis that the APRN can use throughout clinical practice.