Prostate-specific antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer; however, the significance of PSA at or near the time of death is not well understood. This study aimed to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC). The Mount Sinai Genitourinary Cancer Biorepository, an institutional review board–approved, single-institution database containing all consented genitourinary cancer patients seen between 2010 and 2018, was used to identify and stratify patients into the following cohorts based on their PSA at or near death: <100 ng/mL, 100–1000 ng/mL, and >1000 ng/mL. Analyses were performed to assess clinical characteristics of disease, treatment response, and outcomes. We identified 1097 patients with prostate cancer, and 101 were confirmed to be deceased following a diagnosis of mCRPC. In patients with mCRPC, cohorts of higher PSA level at death were associated with lower Gleason score at diagnosis and a trend toward longer time to mCRPC and longer time from diagnosis to death, despite a higher burden of disease at death. Conversely, subgroup analysis of PSA < 10 ng/mL at death was associated with lower rates of imaging within 6 months of death, lower treatment rate, and worse clinical outcomes. Cohorts of different PSA levels at death in mCRPC patients showed distinct patterns of disease characteristics and clinical outcomes, likely due to the underlying molecular phenotype differences. Imaging for the patient population with very low PSA levels may be underutilized and should be considered more routinely. In this article, we characterize metastatic castration-resistant prostate cancer (mCRPC) based on the patients’ prostate-specific antigen at death through retrospective analysis (N = 101). We found distinct patterns of disease characteristics and clinical outcomes, likely due to the underlying molecular phenotype differences. Furthermore, it may be important to consider routine imaging, particularly for those exhibiting characteristics of neuroendocrine differentiation.