Well-differentiated neuroendocrine carcinoma (WDNC) of the lower respiratory tract displays clinical and radiologic features intermediate between carcinoids and small cell carcinoma and shares some biologic characteristics with both. We describe a case of WDNC resistant to three different treatments. The patient, a 42-year-old woman, received 2 cycles of chemotherapy before coming to our observation, including cyclophosphamide, adriamycin and vincristine, with progression of disease. We administered r-alpha-2a interferon for 2 months, but the patient showed clinical progression. Therefore, streptozotocin associated with epirubicin was utilized, but the patient died of disease progression after 4 cycles and 10 months from the first treatment. The case of WDNC described in this report showed an unusual aggressive clinical course and was refractory to conventional and unconventional treatments. The proper management for WDNC is still unknown. However, according to literature data, the chemotherapeutic schemes employed for small cell lung cancer represent the first treatment choice for WDNC. Further studies are needed to help define treatment strategies according to the biology of the tumor.