Abstract The gonadal health status of the chocolate clam Megapitaria squalida collected from the Santa Rosalía mining port and San Lucas beach (reference site), Gulf of California, Mexico, was assessed through histological analysis of the reproductive tissue, from which the histopathological alteration index (HAI) was determined. In addition, copper and iron accumulation in tissue was revealed using histochemical techniques. Our results showed a large presence of copper (30%) and iron (45%) only in the gonad tissue of clams from Santa Rosalía, in which histopathological alterations observed were inflammatory responses, degenerative–progressive processes, cell death, and response to infectious agents. The HAI was significantly higher in Santa Rosalía specimens (mean ± SE, 72.18 ± 6.12) than in San Lucas clams (4.60 ± 1.07). At San Lucas beach, a higher prevalence of histopathological alterations occurred in clams in the spent stage (43.2%) and in autumn (18.4%) and winter (17.8%) in concordance with the normal reproductive rest period, whereas at Santa Rosalía a higher prevalence occurred in clams at the ripe stage (76.9%) and in spring (83.7%). In conclusion, our results showed the deteriorated health condition of gonads in M. squalida from the Santa Rosalía mining port, which suggests there is a relationship with chronic exposure to local high levels of heavy metals. The high prevalence and intensity of histopathological alterations in the gonad suggest a strong adverse effect on gametogenesis, gamete quality, and, ultimately, in the reproductive potential of M. squalida at this site.