Primary adrenal lymphoma (PAL) is difficult to distinguish from other adrenal masses. Soluble interleukin-2 receptor (sIL-2R) is a diagnostic biomarker for nodal non-Hodgkin lymphoma, whose association with PAL is unknown.The aim of this study was to determine the diagnostic utility of serum sIL-2R for Patients with PAL.Prospective cohort study.A total of 118 patients with adrenal masses who were willing to be tested for levels of serum sIL-2R from a tertiary hospital between 2019 and 2021 were included.Serum sIL-2R and lactate dehydrogenase (LDH) levels.Patients with PAL had significantly higher sIL-2R levels than those of patients with other adrenal masses with indetermined and benign computed tomography (CT) features (both Ps < 0.001). The LDH levels of patients with PAL were also significantly higher than those of patients with other adrenal masses with indeterminate and benign CT features (both Ps < 0.001). Good discrimination of patients with PAL from other patients (PAL vs other adrenal masses with indeterminate CT features/non-PAL) was achieved with an area under the receiver operating characteristic curve (AUC) of 0.984 (95% CI, 0.95-1)/0.992 (95% CI, 0.975-1.000) using the serum levels of sIL-2R and further improved (AUC = 0.998, 95% CI, 0.994-1.000; AUC = 0.999, 95% CI, 0.996-1.000) after adjusting by LDH category.For the first time, we have identified that serum sIL-2R and LDH category-adjusted sIL-2R levels have good diagnostic performances for PAL.© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.