ABSTRACT Circulating galactomannan antigen detection plays an important role in the diagnosis of histoplasmosis and blastomycosis. Historically, clinical laboratories have offered separate, genus-specific antigen detection assays across different specimen types for these two dimorphic pathogens. However, given their substantial geographic overlap, similar clinical presentation, comparable treatment approaches, and well-described antigenic cross-reactivity, the clinical rationale for maintaining separate, genus-specific antigen detection assays is increasingly unclear. In this Commentary, we propose that a combined, genus-agnostic Histoplasma / Blastomyces antigen detection assay represents a practical, evidence-aligned approach for diagnostic evaluation of these endemic mycoses.