Purpose: Histopathologic analysis of femoral head specimens following total hip arthroplasty (THA) is a routine practice that represents a significant use of health care resources. However, it occasionally results in discovery of undiagnosed hematopoietic malignancy and other discrepant diagnoses such as avascular necrosis. The purpose of this study was to determine the rate of discordant and discrepant diagnoses discovered from routine histopathological evaluation of femoral heads following THA and perform a cost analysis of this practice. Materials and Methods: A review of patients undergoing primary THA between 2004-2017 was conducted. A comparison of the surgeon’s preoperative and postoperative diagnosis, and the histopathologic diagnosis was performed. In cases where the clinical and histopathology differed, a review determined whether this resulted in a change in clinical management. Medicare reimbursement and previously published cost data corrected for inflation were utilized for cost calculations. Results: A review of 2,134 procedures was performed. The pathologic diagnosis matched the postoperative diagnosis in 96.0% of cases. Eighty-three cases (4.0%) had a discrepant diagnosis where treatment was not substantially altered. There was one case of discordant diagnosis where lymphoma was diagnosed and subsequently treated. The cost per discrepant diagnosis was $141,880 and per discordant diagnosis was $1,669 when using 100% Medicare reimbursement and Current Procedural Terminology (CPT) code combination 88304+88311. Conclusion Histopathologic analysis of femoral head specimens in THAs showed an association with high costs given the rarity of discordant diagnoses. Routine use of the practice should be at the discretion of individual hospitals with consideration for cost and utility thresholds.