Inorganic mercury, in the form of mercurous chloride, or calomel, is intentionally added to some cosmetic products sold through informal channels in Mexico and the US for skin lightening and acne treatment. These products have led to multiple cases of mercury poisoning but few investigations have addressed the contamination of cream users’ homes. We report on several cases of mercury poisoning among three Mexican-American families in California from use of mercury-containing skin creams. Each case resulted in widespread household contamination and secondary contamination of family members. Urine mercury levels in cream users ranged from 37 to 482 µg/g creatinine and in non-users from non-detectable to 107 µg/g creatinine. Air concentrations of up to 8 µg/m3 of mercury within homes exceeded the USEPA/ATSDR health-based guidance and action level of <1.0 μg/m3. Mercury contamination of cream users’ homes presented a multi-pathway exposure environment to residents. Homes required extensive decontamination, including disposal of most household items, to achieve acceptable air levels. The acceptable air levels used were not designed to consider multi-pathway exposure scenarios. These findings support that the calomel is able to change valence form to elemental mercury and volatilize once exposed to the skin or surfaces in the indoor environment.