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Hansen's disease, commonly known as leprosy, is a chronic mycobacterial infection caused by Mycobacterium leprae. Although generally uncommon in the United States, it is endemic in the Southern United States. We diagnosed and managed five leprosy patients from Northwest Louisiana, each presenting a distinct set of challenges. A retrospective study was performed to collect demographic, clinical, and laboratory data from our cases. The information was analyzed with a specific focus on associated factors, diagnosis, and management. The mean age at diagnosis was 67.6 years (range 56–83 years), and the average delay in diagnosis was 8.4 months (range 1–20 months). All five patients presented with nonhealing rashes, and three initially sought help from primary care providers. Only two patients developed subjective numbness. Leprosy was not suspected before skin biopsy in three cases, while noninfectious diagnoses were considered, including mycosis fungoides, erythema multiforme, vasculitis, and amyloidosis. In the other two cases, leprosy was in the initial differential diagnosis. Ultimately, the diagnosis of leprosy was established in all five individuals based on clinical presentation, routine histopathology, and tissue acid-fast staining. This case series highlights the importance of leprosy, especially in the Southern United States where its incidence is increasing.