Melanocytic nevi of palms and soles (MNPS) cause diagnostic problems to dermatopathologists because they share histologic features with malignant melanoma (MM). Early MNPS frequently display a striate appearance, suggesting that, in this subset of nevi, both melanocytes and melanin might have a particular distribution in relation to dermatoglyphics. To verify this hypothesis, we undertook a histological study on 78 junctional MNPS sampled along a plane either perpendicular or parallel to dermatoglyphics. Histologic examination revealed symmetry in 56% of the lesions, circumscription in 60%, intraepidermal scatter of melanocytes in 79%, and melanin columns in 61%. Interestingly, comparison between histologic features of nevi sampled perpendicularly and those of nevi cut parallely to dematoglyphics showed that features of benignity, namely symmetry, circumscription and melanin columns, were significantly more frequent in lesions dissected along a perpendicular plane. Moreover, in 70% of perpendicular samples, intraepidermal scatter of melanocytes and melanin columns were strictly concentrated in furrows. Therefore, to avoid diagnostic pitfalls in the differentiation between junctional MNPS and MM, we strongly suggest to dissect MNPS along a plane perpendicular to skin markings. We hypothesize that mechanical stress can be responsible for concentration of intraepidermal scatter of melanocytes and melanin columns in skin furrows.