Here, we report the clinico-pathological findings of Buruli ulcer. The patients were 2 females, 9 and 23 years of age and one male, 47 years of age from the Ashanti Country of Ghana. Clinically, cutaneous lesions were classified as nodular, ulcero-nodular and ulcerative. Histopathologically, lesions involved cutaneous and subcutaneous tissue, which showed lympho-epithelioid cell proliferation and panniculitis with characteristic fat necrotic changes. Vascular inflammation, with the nerve tissue involvement, are prominent features on the chronological spectrum of the 3 cases. In all but the early case, Mycobacterium ulcerans could be visualized from the mid dermal area to the subcutis by Fite-Faraco and Harada stain. The ulcerated lesions were also immunoreactive to phenolic glycolipid-1 (PGL-1). These findings suggest Mycobacterium ulcerans infection with lesions of different ages. Further, we also show the need to identify distinct characteristics for differential diagnosis with lesions caused by other mycobacteria.