In 2018 about 5.5 million US residents used cocaine. The most used route of administration for the drug is intranasal inhalation and thus the adverse effects of cocaine on the nasal tract are very common. Habitual nasal insuf- flations of cocaine may cause mucosal lesions, and if cocaine use becomes chronic and compulsive, progressive damage of the mucosa and perichondrium leads to ischemic necrosis of septal cartilage and perforation of the nasal septum. Occasionally, cocaine-induced lesions cause extensive destruction of the osteocartilaginous structures of nose, sinuses and palate that can mimic other diseases such as tumors, infections, and immunological diseases. Thorough diagnostic workup, including endoscopic, radiologic, histopathologic and serologic testing is imperative to arrive at the proper diagnosis and to initiate appropriate local and systemic treatment. Positive antineutrophil cytoplasmic antibody (ANCA) test results may be found in an unexpectedly large proportion of patients with cocaine induced midline destructive lesions (CIMDL). The presence of these HNE-ANCA seems to promote or define the disease phenotype. A genetic predisposition might cause such lesions, which are observed in a minority of cocaine abusers. CIMDL do not respond well to immunosuppressive therapy. Only the consistent removal of persistent stimuli of autoantibody production (cocaine, bacterial superinfections) can halt the disease process, prevent the progression of the lesions and promise success of surgical repair procedures