Background: Diagnosis of endometriosis and evaluation of incidence data are complex tasks because the disease is identified laparoscopically and confirmed histologically. Incidence estimates reported in literature are widely inconsistent, presumably reflecting geographical variability of risk and the difficulty of obtaining reliable data. Methods: We retrieved incident cases of endometriosis in women aged 15–50 years using hospital discharge records and pathology databases of the Friuli Venezia Giulia region in the calendar period 2004–2017. We studied the spatial pattern of endometriosis incidence applying Bayesian approaches to Disease Mapping, and profiled municipalities at higher risk controlling for multiple comparisons using both q-values and a fully Bayesian approach. Results: 4125 new cases of endometriosis were identified in the age range 15 to 50 years in the period 2004–2017. The incidence rate (x100 000) is 111 (95% CI 110–112), with a maximum of 160 in the age group 31–35 years. The geographical distribution of endometriosis incidence showed a very strong north-south spatial gradient. We consistently identified a group of five neighboring municipalities at higher risk (RR 1.31 95% CI 1.13; 1.52), even accounting for ascertainment bias. Conclusions: The cluster of 5 municipalities in the industrialized and polluted south-east part of the region is suggestive. However, due to the ecologic nature of the present study, information on the patients’ characteristics and exposure histories are limited. Individual studies, including biomonitoring, and life-course studies are necessary to better evaluate our findings.