Complete response can be difficult to assess after isolated limb perfusion (ILP) for metastatic in-transit melanoma, especially when numerous and unresectable post-necrotic persisting pigmented lesions occur. These residual lesions are mainly seen in the more superficial and pigmented types of metastatic disease and correspond to the residual melanophage granuloma that persists after tumor tissues undergo complete necrosis. Reflectance confocal microscopy (RCM) is a non-invasive technique that allows the exploration of the superficial dermis. Here, we present the case of a patient in whom numerous post-ILP limb residual pigmented lesions were explored using combined RCM and histological examination of sample lesions and could be characterized as non-active. This approach allowed us to avoid additional excisions.