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Objective: Acculturation discrepancy occurs when the rate of host culture acquisition and/or heritage culture retention between non‐native parents and their children diverges. The resulting conflict may exacerbate mental health conditions in already vulnerable populations. The present study examined discrepancies between Hispanic and Anglo‐American acculturation, as two separate constructs, and mental health symptomology in Hispanic childhood cancer survivors (HCCS) and their parents. Methods: Participants were 68 matched parent‐child dyads (HCCS (Mage = 19.4 (2.77) years., 50.0% female); and parent (Mage = 46.3 (6.07) years., 89.7% female)). Study variables were HCCS posttraumatic‐growth (PTG) and quality‐of‐life (PedsQL); parent posttraumatic stress (PTSD); and parent/HCCS depressive symptoms (CESD) and acculturation orientations. Discrepancy was calculated as the dyadic difference between like acculturation measures. Results: After controlling for covariates, Hispanic acculturation discrepancy and HCCS psychosocial health (a subset of PedsQL) was negatively correlated (r = −0.26, p < 0.5); while Anglo‐American acculturation discrepancy was positively associated with HCCS PTG (r = 0.34, p < 0.01) and overall PedsQL (r = 0.24, p < 0.05), and moderated the relationship between parent CESD and HCCS PedsQL. Conclusion: The findings suggest that the two acculturation discrepancy constructs have opposite effects. HCCS losing their heritage culture while their parents simultaneously retain it appears to be a deleterious process; whereas, HCCS learning the US culture more rapidly than parents may have protective benefits. This study has important implications for mental health interventions among HCCS. Findings should be used to inform the survivorship clinical community of the value of acculturation timing and parent/child discrepancy. [ABSTRACT FROM AUTHOR]