OBJECTIVES: The aim of this study was to measure the tissue sodium concentration (TSC) within tumors and normal prostate in prostate cancer patients, using prostatectomy as pathological criterion standard. MATERIALS AND METHODS: Fifteen patients with biopsy-proven, magnetic resonance imaging (MRI) visible, intermediate- or high-risk prostate cancer underwent a dedicated research sodium MRI, before treatment with radical prostatectomy. All participants signed written informed consent for this institutional review board-approved prospective study. 3 T MRI acquired using a dedicated multinuclear clamshell transmit coil and a bespoke dual-tuned H/Na endorectal receive coil, with intracellular-sodium imaging acquired using inversion recovery sequences; a phantom-based calibration enabled quantitative sodium maps. Regions of interest were defined for normal peripheral zone (PZ) and transition zone (TZ) and tumor regions, referenced from histopathology maps. A 1-way analysis of variance compared normal and tumor tissue, using Tukey test for multiple comparisons. RESULTS: Two patients were excluded due to artifact; software error resulted in 1 further intracellular-sodium failure. Fifteen tumors were detected (13 PZ, 2 TZ) in 13 patients: Gleason 3 + 3 (n = 1), 3 + 4 (6), 3 + 5 (2), 4 + 3 (5), 4 + 5 (1). Both mean TSC and intracellular-sodium were significantly higher in normal PZ (39.2 and 17.5 mmol/L, respectively) versus normal TZ (32.9 and 14.7; P < 0.001 and P = 0.02). Mean TSC in PZ tumor (45.0 mmol/L) was significantly higher than both normal PZ and TZ tissue (P < 0.001). Intracellular sodium in PZ tumors (19.9 mmol/L) was significantly higher than normal TZ (P < 0.001) but not normal PZ (P = 0.05). Mean TSC and intracellular-sodium was lower in Gleason ≤3 + 4 tumors (44.4 and 19.5 mmol/L, respectively) versus ≥4 + 3 (45.6 and 20.2), but this was not significant (P = 0.19 and P = 0.29). CONCLUSIONS: Tissue sodium concentration and intracellular sodium concentrations of prostate tumors were quantified, with PZ tumors demonstrating a significantly increased TSC.