The present invention concerns a molecular signature of cutaneous pigmentary spots, comprising the genes MXRA5, LYZ, CTSL2, PLAU, TIMP1, EFEMP1, ECM1, ASPN, HS3ST6, PAPLN, CHSY1 and FLRT2, and various applications of this signature. In particular, the invention concerns a method for characterizing a known or suspected pigmentary spot in a human being, comprising comparing the levels of expression in skin samples obtained from said spot and from adjacent undamaged skin, of at least one dermal gene linked to matrix remodelling or to its extracellular proteoglycan and glycoprotein components, selected from the list constituted by the genes MXRA5, LYZ, CTSL2, PLAU, TIMP1, EFEMP1, ECM1, ASPN, HS3ST6, PAPLN, CHSY1 and FLRT2. The invention also concerns methods for evaluating the efficacy of a pigmentary spot treatment, cosmetic and therapeutic methods for the treatment of pigmentary spots, and various modulators for said genes, and their use.