OBJECTIVES: To investigate the clinical characteristics of women with superficial peritoneal endometriosis (SUP) diagnosed by surgery and not confirmed by histology, compared with histologically proven SUP. DESIGN: Single-center, nested case-control study. Participants/Materials: Patients with a surgical report of SUP (n = 390), comprising a subgroup with histological confirmation of endometriosis (n = 245) and a subgroup without it (n = 145). In addition, we enrolled a control group (n = 390) among non-pregnant patients submitted to a laparoscopy or laparotomy for a benign gynecologic condition without any macroscopic sign of endometriosis. SETTING: University hospital. METHODS: Data synthesis, descriptive statistics, chi-square test and one-way analysis of variance followed by Tukey's test. RESULTS: All groups had similar age, body mass index, smoking prevalence, serum AMH levels and menstrual cycle patterns. However, the two SUP subgroups had the same prevalence and intensity of endometriosis symptoms. The SUP/histology-negative subgroup was more likely to have a familial history of endometriosis (14% vs. 1%) or a personal history of primary infertility (29% vs. 19%) or primary dysmenorrhea (50% vs. 33%) compared to the control group (all p values <
0.01). The intensity scores for dysmenorrhea, deep dyspareunia and non-cyclic chronic pelvic pain were severer in both SUP subgroups than in the control group (p<
0.05). LIMITATIONS: The participants underwent surgery, so their symptoms may not represent groups with initial or mild disease that responded to medical treatments. Due to the retrospective design, performance bias cannot be ruled out. CONCLUSIONS: Patients with suspected SUP lesions and a negative histology had clinical characteristics resembling those with proven endometriosis. Further characterization with molecular biomarkers is needed to explain why these women are so symptomatic in the absence of histological hallmarks of the disease.