In a retrospective analysis of biopsies from January 1, 2019 to December 31, 2020, at University Hospitals Cleveland Medical Center, we aimed to determine the frequency of dermatologic conditions biopsied in African Americans (AA). Given that AAs constitute 13.4% of the US population, understanding the skin disease profile within this significant demographic is crucial. From a total of 1701 biopsies collected from 1442 AA patients, benign neoplasms emerged as the most common diagnosis, accounting for 26.7%, predominantly in females. Notably, cutaneous T-cell lymphoma was the most frequently biopsied malignancy, whereas pigmentary disorders were the least common at 1.4%. The study highlighted the higher occurrence of squamous cell carcinoma compared with basal cell carcinoma in AA, contrasting trends in other racial demographics. Moreover, recognizing the unique presentations of skin disorders in different racial backgrounds is essential, especially because disparities have been reported in skin of color training among dermatology residency programs. Understanding these racial differences in skin diseases can assist clinicians in refining their diagnostic approach. Future research could further explore the potential gaps between clinical expectations and histologic findings, improving diagnostic accuracy.