BACKGROUND : Small-cell lung cancer (SCLC) is a type of fatal tumor that is increasing in prevalence. While these are unpleasant facts to consider, it is vitally important to be informed, and it is important to catch the disease early. Typically, lung cancer does not show severe clinical symptoms in the early stage. Once lung cancer has progressed, patients might present with classical symptoms of respiratory system dysfunction. Thus, the prognosis of SCLC is closely related to the early diagnosis of the disease. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is related to cancer occurrence, especially for SCLC with the presence of Cushing's syndrome, which is dependent on markedly elevated ACTH and cortisol levels. METHODS : In the current report, we describe two middle-age patients who were originally diagnosed with diabetes mellitus with no classical symptoms of lung cancer. The patients were eventually diagnosed with SCLC, which was confirmed by bronchoscopic biopsy and histopathology. SCLC-associated diabetes was related to EAS, which was an endogenous ACTH-dependent form of Cushing's syndrome with elevated ACTH and cortisol levels. Multiple organ metastases were found in Patient 1, while Patient 2 retained good health at 2 years follow-up. EAS symptoms including thyroid dysfunction, hypercortisolism and glucose intolerance were all resolved after anticancer treatment. CONCLUSIONS : In conclusion, SCLC might start with diabetes mellitus and increased cortisol and hypokalemia or other EAS symptoms. These complex clinical features were the most significant factors to deteriorate a patient's condition. Early diagnosis and treatment from clinicians were essential for the anti-cancer treatment for patients with SCLC.