Abstract Disclosure: V.B. Brondani: None. A.M. Griffin: None. T.J. Owen: None. K.W. Merriman: None. J.M. Varghese: None. C. Jimenez: None. S.G. Waguespack: None. P.H. Graham: None. M.T. Campbell: None. M.M. Hassan: None. M.A. Habra: None. Background: Adrenocortical carcinoma (ACC) is a rare malignancy with an annual incidence of 0.102 cases per 100,000 persons per year in the United States. At our tertiary cancer center, we have observed increasing numbers of cases, but to date there has been no study exploring ACC incidence at a populational level to validate our observations. Furthermore, the possibility of geographic ACC clusters has not been studied. Our objectives were to evaluate the incidence and geographical distribution of ACC cases in Texas. Methods: Cases of ACC between 2000 and 2018 were retrospectively identified from the Texas Cancer Registry (TCR). Cases were registered in 110 of Texas' 254 counties (43.3%), representing 92.74% of the total population of Texas. SEER Stat software was used to pool demographic and clinical characteristics and calculate incidence rates. Kaplan-Meier overall survival curve and Pearson's correlations were calculated using SPSS. P values < .05 were considered significant. ACC county-level heatmaps were created with Tableau software to identify clusters. Breast, prostate, lung cancer incidences and their geographic distribution were compared to ACC data. Results: TCR registered 448 cases of ACC in the study period, with a median of 23 new cases/year (range 14-33). Thirty-three (7.4%) patients were aged 19 years or younger (15 were under 5 years), 293 (65.4%) patients were between 20 and 64 years, and 122 (27.23%) were 65 years or older. The majority were female (270 cases [60.3%]), and White (393 [87.7%]). One hundred (22.3%) patients were Hispanic. In 155 evaluable cases, the proportions of patients with stage I, II, III, and IV disease at diagnosis were 7.7%, 27.7%, 16.1%, and 48.4%, respectively. The median overall survival was two years (range, 0-19 years). The mean adjusted population ACC incidence rate was 0.104 per 100,000 per year (std = 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each (median, 34 cases per county; range, 11-66) and a median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county (median, 1 case; range, 1-9 cases). The highest SIRs (corresponding to >10, range, 11.2-30.8) were found in counties with a median population of fewer than 14,000 and with only one reported case. We could not detect any geographic clustering of ACC. Counties with a high frequency of breast, prostate, lung cancer cases also had more cases of ACC (Pearson correlation .982, .981, and .982, respectively; P < .01 for all tests). Conclusion: The incidence of ACC in Texas remained relatively stable through the years and consistent with the US annual incidence. We did not observe any obvious ACC cluster, and SIRs may not be useful for analyzing this rare disease. Presentation: Friday, June 16, 2023