Abstract:  Proteins of the a disintegrin and metalloprotease (ADAM) family are transmembrane proteins involved in ectodomain shedding and in cellular interactions. In skin, ADAM‐15 is detected in the epidermis and dermal vascular structures by immunolocalization. Expression is also detected in isolated fibroblast, keratinocytes and endothelial cells in culture. Despite high expression of ADAM‐15 throughout the wound repair process, wound healing experiments in vivo revealed a dispensable role of ADAM‐15 for the healing process. No alterations in wound closure, re‐epithelialization, contraction, scar formation and angiogenesis were detected in animals carrying ADAM‐15−/− deletion. When analysing melanoma development by grafting melanoma cells into the flank of ADAM‐15−/−, no significant alteration in tumor growth was detected. However, at later stages, melanomas in the ADAM‐15−/− animals were smaller than those grown in WT animals. At all time points, no significant differences in vascularization of the peritumoral stroma and tumors were detected. Interestingly, we could detect a reduced number of metastasized lungs and lymph nodes in ADAM‐15−/− animals as compared to control littermate mice. In conclusion, our study indicated that ADAM‐15 is dispensable for cutaneous wound healing and B16F1 melanoma growth, but significantly contributes to metastasis formation.