Investigate if the knowledge of the anatomic distribution of histologically proved deeply infiltrating endometriosis (DIE) lesions contributes to understand pathogenesis. Observational study between June 1992 and December 2004 (retrospective study between 1992 and 2000; prospective study between 2001 and 2004). Continuous series of 426 patients suffering from pelvic pain who underwent complete surgical exeresis for DIE. DIE lesions were classified according to four different possibilities: (1) DIE lesions were classified as located in the anterior or posterior pelvic compartment. By definition anterior DIE was defined as bladder DIE and posterior DIE included the other pelvic DIE locations: uterosacral ligament (USL), vagina, ureter and intestine. (2) DIE were classified as left, median and right. By definition we classified as left DIE lesions the following (left USL, left ureter, sigmoid colon, descending colon), as median DIE lesions the following (bladder, vagina, rectum, rectosigmoid junction, transverse colon, small intestine, omentum) as right DIE lesions the following (right USL, right ureter, ascending colon, appendix, ileocecum junction). (3) DIE lesions were classified as pelvic or abdominal. We classified as abdominal DIE lesions the following: descending colon, transverse colon, ascending colon, appendix, ileocecum junction, small intestine, and omentum. All the other DIE locations (bladder, USL, vagina, ureter, rectum, rectosigmoid junction, sigmoid colon) were considered as pelvic DIE lesions; (4) DIE lesions that could presented right and/or left distribution (ureter, USL, …) were classified as unilateral or bilateral. These 426 patients presented 759 histologically proved DIE lesions: bladder (48 lesions; 6.3%); USL (400 lesions, 52.7%); vagina (123 lesions, 16.2%); ureter (16 lesions, 2.1%); intestine (172, 22.7%). Pelvic DIE lesions are significantly more often located in the posterior compartment of the pelvis (682 DIE lesions (93.4%) versus 48 DIE lesions (6.6%); p < 0.0001). Pelvic DIE lesions are significantly more frequently located on the left side. Patients with unilateral pelvic DIE lesions the anatomic distribution is significantly different in the three groups: left (172 lesions; 32.0%), median (284 lesions; 52.8%) and right (82 lesions; 15.2%) (p < 0.0001). Patients with lateral lesions, left DIE lesions (172 lesions; 67.8%) were found significantly more frequently than right DIE lesions (82 lesions; 32.2%) (p < 0.0001). A similar predisposition was observed when we included patients with bilateral pelvic DIE lesions (p = 0.0031). The same significantly asymetric distribution is observed for total (pelvic and abdominal) DIE lesions. Our results demonstrate that distribution of DIE lesions is asymmetric. It is possible that this is related to the anatomical difference of left and right hemipelvis and to flow of peritoneal fluid. These findings support the hypothesis that retrograde menstruation following by implantation of regurgitated endometrial cells is implicated in the pathogenesis of DIE.