Recent studies revealed a negative association between acculturation and sun-safe behaviors, possibly mediated by education level, health status, and social networks. We sought to elucidate this relationship by exploring the moderating effects of gender and health insurance on each mediated path. We used data from 496 Latino respondents to the 2005 Health Information National Trends Survey. Acculturation, assessed by a four-item index, was the primary predictor; use of sunscreen and protective clothing were the primary outcomes, assessed by frequency scales. Moderated mediation was tested with an established causal moderation method. The mediated association between acculturation, education level and sunscreen use might be stronger among women than men (P < 0.08). We found no evidence of moderated mediation for use of protective clothing. The findings suggest ways of refining the theoretical and empirical rationale for sun safety research and interventions with Latinos. Studies should replicate these models with longitudinal data.