The known range of the oyster pathogen Haplosporidium nelsoni Haskin, Stauber, and Mackin (MSX) extends along the North American Atlantic coast from Nova Scotia to Florida. Our study demonstrates that H. nelsoni is also present throughout the Gulf of Mexico. Thirty of 41 oysters (73%) sampled from sites ranging from Florida to as far south as Venezuela were positive for MSX by PCR amplification of the ribosomal rRNA gene complex. DNA sequences cloned from oysters positive for H. nelsoni were ≥99% identical to H. nelsoni and clearly divergent (<89% identical) from known haplosporidian congeners, including Haplosporidium costalei Wood and Andrews (SSO). The absence of MSX epizootics in the Gulf of Mexico, despite the wide distribution of H. nelsoni infections, raises questions about pathogenicity and the host-parasite relationship in subtropical latitudes.