Pathologic fractures are associated with poor outcomes. This article investigated the prevalence of underestimation of risk by the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Surgical Risk Calculator (SRC) in patients with pathologic humerus fractures. Two hundred seven (207) patients were identified and analyzed using the ACS-NSQIP SRC. Predicted and actual outcomes were then compared. Average hospitalization was 6 ± 10 days. Ten patients (5%) had a mild adverse event (AE), and 15 (7%) had a serious AE. The ACS-NSQIP SRC underestimated hospitalizations (p < 0.001), but not serious AE (p = 0.601), mild AE (p = 0.948), cardiac complications (p = 0.817), pneumonia (p = 0.713), surgical site infection (p = 0.692), urinary tract infection (p = 0.286), venous thromboembolism (p = 0.554), acute renal failure (p = 0.191), discharge to acute care facility (p = 0.865), readmission (p = 1.0), reoperation (0.956) or mortality (p = 0.872). Negative outcomes were limited in this cohort, and the SRC demonstrated acceptable accuracy. Future investigation of the calculator in other orthopaedic populations is warranted. (Journal of Surgical Orthopaedic Advances 28(4):250-256, 2019).