We report the case of a primary cutaneous melanoma with acantholytic-like changes in a 61-year-old man. Clinical and immunohistochemic features were similar to those of other superficial spreading with vertical growth melanomas. Histologically, intraepidermal and suprabasal bullous spaces were filled by isolated tumor cells, simulating acantholytic blisters. These findings could be explained by the presence of inflammation-related extracellular fluid. Two other cases with suprabasal discohesive atypical melanocytes have recently been described. We report the first case of malignant melanoma with an intense and diffuse pattern of dyscohesion, resembling acantholysis. Recognition of this histologic pattern in malignant melanoma is important to avoid a misdiagnosis.