Toxoplasma gondii infects up to one-third of the world's population, making it the protozoan that most infects people worldwide. Among the forms of presentation of toxoplasmosis, hepatitis is probably the least frequent with only a few case reports in the world's medical literature. Despite the fact that the first diagnostic test is the serology using the ELISA technique because its sensitivity is close to 100% in our case, it was reported negative. The biopsy gave the definitive diagnosis, and we were able to start treatment immediately. Although the first line of treatment is sulfadiazine and pyrimethamine, our sulfate allergic patient received an alternative regimen of doxycycline, clindamycin, and azithromycin with a good response. This is the only case of Toxoplasma hepatitis reported in Mexico and the only one in the world with negative serology with a good response to second-line treatment.