BACKGROUND: Uterine leiomyomas rarely cause pseudo-Meigs' syndrome with elevated serum CA 125 levels. CASE: A 39-year-old patient with a large uterine leiomyoma is described. The associated massive ascites, pleural fluid, and increased CA 125 level all seemed to be related to the uterine tumor. Hydropic degenerating leiomyomas are characterized by focal accumulation of edema and collagen deposition. Marked degrees of hydropic degeneration may have resulted in cystic degeneration, leading to large myometrial cysts. A presumed direct relation between the abundance of intratumoral fluid and presence of ascites seemed justified. The increased level of CA 125 most probably resulted from the peritoneal mechanical irritation from the large leiomyoma or from a large volume of ascites. Having accumulated a sufficient volume and pressure, the ascites finds it way through the diaphragm through intercellular gaps and diaphragmatic apertures, as well as through small bilateral areas where muscular tissue of the diaphragm is replaced by areolar tissue, resulting in the presence of pleural fluid. CONCLUSION: The pathophysiology of a uterine leiomyoma mimicking a pelvic malignancy is described.