Abstract Background In the United States, sepsis is responsible for 9% of all cancer-related deaths. Patients with cancer presenting with sepsis have worse outcomes, which is probably because of immunosuppression, due to the disease burden itself or the effects of chemotherapy. Biomarkers are noninvasive rapid diagnostic tools, assisting in the early diagnosis of patients with suspected sepsis. The identification of a biomarker with reasonable sensitivity and specificity for early sepsis could potentially result in a beneficial effect on clinical outcomes in these patient populations. Procalcitonin (PCT) is a promising marker for identification of bacterial infections, but its role in oncology populations has less been studied. We investigated the performance characteristics of sepsis biomarkers for diagnosis of verified bacterial sepsis. Methods This was a retrospective study of patients admitted between June 1, 2018, and January 31, 2019, from the Emergency Department, MD Anderson Cancer Center. Approximately 51% adult patients were diagnosed with sepsis. Sepsis was defined by Surviving Sepsis Campaign (SSC) definitions. Three biomarkers were evaluated based on hospital records: (1) PCT ≥0.08 ng/mL, (2) C-reactive protein (CRP) ≥13 mg/L, (iii) white blood cells (WBCs) ≥11 K/µL. The diagnostic performances of the individual biomarkers were compared using the area under the receiver operating characteristic (ROC) curve (AUC). Results In total, 635 adult sepsis patients were included and investigated during the study period. For diagnosis of bacterial sepsis based on SSC criteria, the analysis yielded a CRP with sensitivity of 71% (95% CI, 56%-86%) and specificity of 22% (95% CI, 15%-29%), respectively. The area under the ROC curve was 52% (95% CI, 41%-68%). The sensitivity of WBCs was 18% (95% CI, 12%-24%), specificity was 84% (95% CI, 71%-97%), and the area under the ROC curve was 51% (95% CI, 43%-68%). However, the PCT reached the sensitivity of 77% (95% CI, 60%-93%) and specificity of 65% (95% CI, 48%-82%), respectively. The area under the ROC curve was 79% (95% CI, 67%-91%), significantly increased. Conclusion In this study, the diagnosis accuracy and specificity of PCT are much higher than those of CRP or WBC in cancer patients. PCT is a useful marker for early detection of sepsis in emergency department patients with suspected infection, especially in cancer patients with neutropenia. Further studies on the role of PCT in this population are warranted.