Differences and similarities in cancer patterns between the country of Mexico and the United States’ Mexican population, 11% of the entire US population, have not been studied. Mortality data from 2008–2012 in Mexico and California were analyzed and compared for causes of cancer death among adult and pediatric populations, using standard techniques and negative binomial regression. A total of 380,227 cancer deaths from Mexico and California were included. Mexican Americans had 49% and 13% higher mortality than their counterparts in Mexico among males and females, respectively. For Mexican Immigrants in the US, overall cancer mortality was similar to Mexico, their country of birth, but all-cancers-combined rates mask wide variation by specific cancer site. The most extreme results were recorded when comparing Mexican Americans to Mexicans in Mexico: with mortality rate ratios ranging from 2.72 (95%CI: 2.44–3.03) for colorectal cancer in males to 0.28 (95%CI: 0.24–0.33) for cervical cancer in females. These findings further reinforce the preeminent role that the environment, in its multiple aspects, has on cancer. Overall, mortality from obesity and tobacco-related cancers was higher among Mexican origin populations in the US compared to Mexico, suggesting a higher risk for these cancers, while mortality from prostate, stomach, and especially cervical and pediatric cancers was markedly higher in Mexico. Among children, brain cancer and neuroblastoma patterns suggest an environmental role in the etiology of these malignancies as well. Partnered research between the US and Mexico for cancer studies is warranted.