Pseudolipomatosis is an artifactual microscopic change in tissues that resembles fatty infiltration, most often described in the gastrointestinal tract. The fatlike spaces represent air or gas bubbles that enter the mucosa through microscopic ruptures secondary to gaseous insufflation. We report a series of cases of pseudolipomatosis encountered in gynecologic tissues removed during hysteroscopic procedures, a finding not previously described. We identified 300 consecutive hysteroscopic procedures performed at our institution from 2006 to 2008. Patients' medical records were reviewed to collect pertinent clinical data. Slides from all cases were systematically reviewed. The diagnosis of pseudolipomatosis was established by consensus. Twenty-eight cases of pseudolipomatosis, representing 9.3% of patients who under went hysteroscopy, were identified. Pseudolipomatosis was found in 9 endometrial curettings or biopsy tissues, 8 endometrial or endocervical polyps, 8 uterine fibroids, 2 fallopian tubes, and 1 endocervical biopsy. The type of distention medium used and length of hysteroscopic procedure did not differ significantly between cases with and without pseudolipomatosis. Pseudolipomatosis vacuoles varied in distribution from crowded clusters to sparsely scattered and solitary. Occasionally, vacuoles were found in vascular channels. Vacuoles were round or ovoid, unilocular, and variable in size. Immunohistochemical staining for adipocyte and endothelial markers were negative. We hypothesize that pseudolipomatosis derives from air that is almost invariably introduced into the uterus during media insufflation for hysteroscopy, creating a bubble under pressure. The air enters tissues either through lining microruptures or during the biopsy procedure. Pseudolipomatosis is a relatively common, easily overlooked finding in hysteroscopically derived specimens that may be misdiagnosed when prominent.