AbstractThe concept of ‘locus minoris resistentiae’ (lmr) is an old but still effective way of thinking in Medicine. In Dermatology, there are many reports of privileged localization of cutaneous diseases on injured skin, which therefore represents a typical condition of lmr. Lately the innovative concept of immunocompromised cutaneous district (ICD) has been introduced to explain why a previously injured cutaneous site may become in time a privileged location for the outbreak of opportunistic infections, tumors, and immune reactions. An ample documentation of multifarious disorders (infectious, neoplastic, immune) appearing in ICDs was delineated by Ruocco et al. in 2009. These cases were grouped according to the clinical settings responsible for the local immune imbalance: regional chronic lymphedema; herpes‐infected sites, which feature the well‐known Wolf's isotopic response; and otherwise damaged areas, comprising sites of vaccination, ionizing or UV radiation, thermal burns, and traumas. In the following five years, what was a “novel” pathogenic concept has been extended to an enlarging variety of clinical conditions. This paper focuses on ICD and the expanding spectrum of this now established pathogenic concept.