Purpose Although much emphasis has been placed on the impact of ambiguity on cognitive processes, the impact of mental health disorder symptoms and racial/ethnic disparities in cancer perception of fatalism and ambiguity remains less explored. This study explored the association between mental health disorder symptoms and negative cancer perceptions. Also, we assessed differences in these outcomes within mental health disorder symptoms and racial/ethnic subgroups. Methods We used the 2019-2020 Health Information National Trends Survey data to assess the perception of cancer fatalism and cancer communication ambiguity, and employed weighted multivariable logistic regression to determine the effects of mental health disorder symptoms on these negative cancer perceptions. Results People with moderate [Adjusted Odds Ratio (AOR)= 1.58, 95% Confidence Interval (CI)= 1.09, 2.31] and severe anxiety/depression (AOR= 1.88, 95% CI= 1.12, 3.14) symptoms were more likely to have cancer fatalism perceptions than people with no anxiety/depression symptoms. People with mild (AOR= 1.33, 95% CI= 1.06, 1.69) or severe (AOR= 1.80, 95% CI= 1.03, 3.16) anxiety/depression symptoms were more likely to perceive cancer communication as ambiguous compared to people who had no anxiety/depression symptoms. Conclusions The study showed that mental health status was associated with both cancer fatalism perception and perceived ambiguity in cancer recommendations. This suggests that interventions aimed at reducing mental health disorder symptoms may potentially reduce perceived cancer fatalism and communication ambiguity, thereby improving participation in cancer prevention programs.