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Introduction: The objectives of the study were to characterize microstructural and mechanical heterogeneity in calcium oxalate monohydrate renal calculi using high-resolution Vickers microhardness testing and to explore potential implications for laser lithotripsy outcomes. Methods: Five pure calcium oxalate monohydrate renal calculi from the same renal calyx were analyzed to ensure chemical equivalence. One stone per pair underwent routine analysis, and its intact companion stone was used for microhardness testing. Composition was confirmed by Fourier-transform infrared spectroscopy. Stones were embedded in epoxy resin, polished with diamond abrasives, hydrated for 24 h, and examined using high-resolution digital light microscopy. Vickers microhardness (HV0.2) was measured on predefined grids using standardized microindentation methodology. Results: Stone diameters ranged from 1.5 to 3 mm. Vickers hardness varied widely (45–180 HV0.2), with mean per-stone values between 76.2 and 137.5 HV0.2. All stones exhibited alternating hard and soft regions without concentric or radial patterns. Conclusions: Calcium oxalate monohydrate renal calculi demonstrate pronounced, irregular microhardness variation. This heterogeneity may explain why some regions dust easily while others resist laser ablation and persist as fragments. Mechanical profiling may serve as a useful adjunct in planning endourological stone treatment.

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