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BACKGROUND In instances of suspected cutaneous infection, standard of care includes obtaining skin biopsies for histology and tissue culture. Few studies have compared the clinical utility of each test. OBJECTIVE To assess the concordance of results between tissue culture and histology, and clinicopathologic features that may influence the diagnostic yield of each test. METHODS A retrospective review of all patients who underwent skin biopsy for histology and tissue culture at New York University from 2013-2018. RESULTS Of 179 patients, 10% had positive concordance, 21% had positive tissue culture only, and 7% had positive histology only. We calculated a kappa correlation coefficient of 0.25 between histology and tissue culture [ref 0.21-0.39=minimal agreement]. Histology exhibited higher sensitivity in detecting fungi, whereas tissue culture was more sensitive in identifying gram-negative bacteria. Antimicrobial use prior to biopsy led to significantly fewer positive cultures (37.5% versus 71%; p=0.023) in patients ultimately diagnosed with infection. LIMITATIONS This study was conducted at a single institution thereby restricting its broad applicability. The lack of a validated gold standard to diagnose infection also limits interpretation of results. CONCLUSION Tissue culture and histopathology often yield discordant results. Dermatologists should recognize specific test limitations, yet high clinical utility in special circumstances, when approaching cases of suspected infection.