Pattern analysis by epiluminescence microscopy of pigmented skin lesions was tested in a study of 318 small pigmented skin lesions that were diagnostically equivocal when examined with the naked eye. An improvement of clinical diagnosis was achieved by epiluminescence microscopy for practically all lesions, both benign and malignant, and was equally impressive for melanocytic and nonmelanocytic lesions. Improvement in diagnostic accuracy was as follows: for small nodular melanomas, from 50% to 70%; for superficial spreading melanoma in situ, from 46% to 80%; for invasive superficial spreading melanoma, from 64% to 90%; and for early lentigo maligna and lentigo maligna melanoma, from 67% to 88%. Conversely, the diagnosis of pigmented Spitz nevi improved from 46% to 93% and of pigmented basal cell carcinomas from 60% to 90%, which appears equally important because most of these lesions had clinically been considered to represent melanomas. The use of epiluminescence microscopy also resulted in considerable improvement in the diagnosis of dysplastic nevi, which was particularly helpful in making therapeutic decisions. Epiluminescence microscopy greatly expands the diagnostic armamentarium available for pigmented skin lesions at a clinical level and thus increases the chances of detecting or ruling out melanoma in its earliest stages.