Cushing's syndrome due to bilateral cortisol-secreting adenomas rarely occurs. We present a case of Cushing's syndrome due to bilateral adenomas. Both adenomas had distinct cell compositions, and were compared with emphasis on immunohistochemical and enzyme histochemical analysis for cytochrome P450(11beta) and 3beta-hydroxysteroid dehydrogenase (3betaHSD). A 37 year-old female was diagnosed with ACTH-independent Cushing's syndrome based on physical findings and hormonal evaluation. High-resolution CT scan showed bilateral adrenocortical adenomas and atrophied glands. 131I-methylnorcholesterol incorporation into both glands suggested both adenomas were functional. Clinical diagnosis prior to surgery was ACTH-independent Cushing's syndrome due to functioning bilateral adenomas. The left adrenal gland was totally resected, while the right one was partially resected by laparoscopic approach. Both adenomas were black on cut sections, and were comparatively evaluated by immunohistochemical and enzyme histochemical analysis for P450(11beta) and 3betaSD. The left adenoma was 1.6 cm in diameter and had a complex cellular composition and enzyme expression similar to that of primary pigmented nodular adrenocortical disease (PPNAD), while the right adenoma was 1.8 cm in diameter with compact cells typical of a solitary cortisol-producing adenoma. Adjacent bilateral adrenal cortex showed marked atrophy, but contained several micronodules. Serum cortisol levels, both at basal and after a low dodexamethasone, normalized thirteen months after surgery. In conclusion, the present case of Cushing's syndrome with bilateral adrenal adenomas demonstrated for the first time the simultaneous occurrence of two distinct adenomas, an ordinary cortisol-producing adenoma and a PPNAD-like adenoma. Further case reports of multiple adrenal adenomas should be well-analyzed to clarify whether the results from this case represent a new subgroup of ACTH-independent Cushing's syndrome.