BACKGROUND: The difficulties in accurately assessing pigmented skin lesions are ever present in practice. The recently described ABCD rule of dermatoscopy (skin surface microscopy at x10 magnification), based on the criteria asymmetry (A), border (B), color (C), and differential structure (D), improved diagnostic accuracy when applied retrospectively to clinical slides. OBJECTIVE: A study was designed to evaluate the prospective value of the ABCD rule of dermatoscopy in melanocytic lesions. METHODS: In 172 melanocytic pigmented skin lesions, the criteria of the ABCD rule of dermatoscopy were analyzed with a semiquantitative scoring system before excision. RESULTS: According to the retrospectively determined threshold, tumors with a score higher than 5.45 (64/69 melanomas [92.8%]) were classified as malignant, whereas lesions with a lower score were considered as benign (93/103 melanocytic nevi [90.3%]). Negative predictive value for melanoma (True-Negative divided by [True-Negative+False-Negative]) was 95.8%, whereas positive predictive value (True-Positive divided by [True-Positive+False-Positive]) was 85.3%. Diagnostic accuracy for melanoma (True-Positive divided by [True-Positive+False-Positive+False-Negative]) was 80.0%, compared with 64.4% by the naked eye. Melanoma showed a mean final dermatoscopy score of 6.79 (SD, +/- 0.92), significantly differing from melanocytic nevi (mean score, 4.27 +/- 0.99; p < 0.01, U test). CONCLUSION: The ABCD rule can be easily learned and rapidly calculated, and has proven to be reliable. It should be routinely applied to all equivocal pigmented skin lesions to reach a more objective and reproducible diagnosis and to obtain this assessment preoperatively.