Abstract Historically recalcitrant to treatment, infection of the nail unit is a pervasive clinical condition affecting about 10%-20% of the U.S. population; patients present with both cosmetic symptomatology and pain, with subsequent dystrophic morphology. To date, the presumptive infectious etiologies include classically-reported fungal dermatophytes, non-dermatophyte molds, and yeasts. Until now, the prevalence and potential contribution of bacteria to the clinical course of dystrophic nails had been relatively overlooked, if not dismissed. Previously, diagnosis had been largely made via clinical presentation, although microscopic examinations (KOH) of nail scrapings to identify fungal agents, and more recently, panel-specific PCR assays have been employed to elucidate causative infectious agents. Each of these tools suffers from test-specific limitations. However, molecular-age medicine now includes DNA-based tools to universally assess any microbe or pathogen with a known DNA sequence. This affords clinicians with rapid DNA sequencing technologies at their disposal. These sequencing-based diagnostic tools confer the accuracy of DNA level certainty, while concurrently obviating cultivation or microbial phenotypical biases. Using DNA sequencing-based diagnostics, the results herein document the first identification and quantification of significant bacterial, rather than mycotic, pathogens to the clinical manifestation of dystrophic nails. In direct opposition to the prevailing and presumptive mycotic-based etiologies, the results herein invoke questions about the very basis for our current standards of care, including effective treatment regimens.