Recent reports show that the sensitivity of endometrial carcinoma detection on liquid-based Papanicolaou (Pap) tests (88%) is considerably higher than that reported on conventional Pap smears (20%-30%), although few laboratories have corroborated these results. We performed a 5-year retrospective review of all liquid-based Pap tests (n = 69) in women who later were given a diagnosis of endometrial carcinoma, performed error root cause analysis, and developed quality improvement initiatives as a means of error reduction. The original and rescreened Pap test sensitivity rates for endometrial carcinoma were 31.9% and 59.3%, respectively. Root cause analysis showed that poor specimen quality and cognitive failures contributed to a false-negative error in 67% (18/27) and 59% (16/27), respectively, of all cases. System analysis showed that latent factors contributing to error included lack of redundant and educational systems. We conclude that system redesign of liquid-based Pap test screening processes has the potential to improve sensitivity in endometrial carcinoma diagnosis.