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Four distinct tumor microenvironments have been proposed based on the expression of programmed death-ligand 1 and the presence of tumor-infiltrating lymphocytes: immunotype I (adaptive resistance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1+); immunotype II (immunologic ignorance, tumor-infiltrating lymphocytes– and programmed death-ligand 1–); immunotype III (intrinsic induction; tumor-infiltrating lymphocytes– and programmed death-ligand 1+); and immunotype IV (tolerance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1–). These subtypes may predict tumor response to immunotherapy. We hypothesized that parathyroid neoplasms may have tumor immunogenic expression that can later be used to guide treatment.We assessed retrospectively the immunohistochemical expression of programmed death-ligand 1 and the presence of tumor-infiltrating lymphocytes (CD3+ and CD8+) and macrophages (CD68+) in parathyroid carcinomas and in atypical parathyroid neoplasms treated at the M. D. Anderson Cancer Center from 1996 to 2016. Using intratumoral digital image analysis, the programmed death-ligand 1 H score was calculated with a standardized formula for predominant staining. The tumor-infiltrating lymphocytes per square millimeter of intratumoral areas were quantified.Within 30 specimens (17 parathyroid carcinomas and 13 atypical parathyroid neoplasms), there was no difference in the median programmed death-ligand 1 H score between the two groups (P = .57). Four parathyroid carcinoma cases had programmed death-ligand 1 H scores ≥1 associated with CD3+ and CD8+ tumor cell density; 2 of them had distant metastases. Parathyroid carcinomas had a lesser median CD3+ density (P = .04) and a lesser median CD8+ density (P =.07) than did atypical parathyroid neoplasms. Median CD68+ density did not differ between groups (P = .22).Parathyroid carcinomas tended to have immune-ignorant and immune-tolerant microenvironments within the neoplasm (immunotypes II and IV). Of the parathyroid carcinoma microenvironments, 17 had patterns of programmed death-ligand 1 and tumor-infiltrating lymphocytes expression (immunotype I), suggesting possible benefit from immunotherapy. In addition, both parathyroid carcinomas and parathyroid neoplasms expressed CD68+. Further exploration of these potential biomarkers as a target in cancer therapies is needed.