Post the coronavirus disease 2019 (COVID-19) pandemic, there arises the concern of a new epidemic as cases of monkeypox are being confirmed, globally. With the initial clinical manifestation of monkeypox resembling that of the common cold or seasonal flu, recognizing alternative differential diagnoses is imperative as a medical health practitioner. The characteristic monkeypox maculopapular rash with the progression to vesicles and pustules before scabbing can be described in several other infections. Understanding the disease progression and distinct clinical presentation of monkeypox in its various stages may allow for a more expedient diagnosis among healthcare providers. Though eradicated, the clinical presentation of smallpox is the most similar to that of monkeypox; however, smallpox is no longer a concern for the general population. Other conditions such as molluscum contagiosum, syphilis, varicella zoster, measles, rickettsialpox, and scabies can present with rashes that may resemble singular or multiple states of the monkeypox rash progression. The ability to correctly diagnose an individual\'s condition promptly may allow healthcare providers to provide correct supportive therapies or treatments.