BACKGROUND Amyloidosis is a devastating multisystemic disease resulting from organ deposition of misfolded proteins and subsequent organ dysfunction. An accurate diagnosis relies frequently on biopsies and microscopy techniques to detect amyloid deposition. We evaluated the diagnostic performance of Congo red staining using polarized light (PM) and fluorescence microscopy (FM) techniques in renal amyloidosis. METHODS We performed a retrospective and prospective analysis of all renal biopsies submitted at a large quarternary hospital in Sydney, Australia, that had undergone PM and FM evaluation using Congo red staining. Identification of amyloid fibrils on electron microscopy was considered the reference method. RESULTS PM and FM displayed very high sensitivity and specificity in correctly identifying amyloid deposits in renal biopsies that tested positive via Congo red staining. Comparison of the diagnostic statistics revealed that they are diagnostically equivalent. CONCLUSIONS In the diagnosis of renal amyloidosis on biopsy, evaluation of Congo red staining may be reliably performed via PM or FM.