We report two cases of a pain syndrome caused by large adrenal metastases in patients with lung cancer. A review of the literature identified 23 previously reported patients with primary lung cancers who appear to have had a similar syndrome, although in none of these cases were other likely causes of the pain syndrome carefully excluded. The syndrome characteristically includes unilateral flank pain but may have abdominal components as well, and has only been reported in patients with large metastases (> or = 5 cm in largest diameter). Although the mechanism by which large adrenal metastases cause the pain syndrome is not clear, we suggest that treatment that includes local anesthetic agents or steroids may be effective. The pain syndrome caused by large adrenal metastases is not included in reviews of cancer pain syndromes but needs to be considered in the differential diagnosis of patients with lung cancer and flank or abdominal pain.