Objective: Over 1 million survivors of multiple primary cancer (MPC) diagnoses reside in the USA. Information regarding their physical and mental health status is limited. This study examined distress and mental health care use among MPC survivors relative to survivors of a single primary cancer (SPC) diagnosis. Methods: Using the 2016 National Health Information Survey, MPC survivors (n = 265), SPC survivors (n = 2103), and no cancer controls (NCC; n = 28,320) were identified. The MPC group was compared to the SPC and NCC groups with regard to multiple distress indices and use of mental health care and anxiety and depression medication. Results: Relative to the SPC group, the MPC group reported more Total Distress (M = 9.59 vs. 8.84; p < .001), and were more likely to report daily or weekly anxiety feelings (OR = 2.07; p < .001), meet criteria for serious psychological distress (OR = 1.49; p = .02) and have talked to a mental health professional (OR = 1.75; p = .01). Comparison of MPC and NweCC groups yielded similar results. The MPC group did not differ from the SPC or NCC groups in severity of anxiety or depression feelings, distress interference, or anxiety and depression medication use. Conclusions: MPC survivors reported greater distress relative to SPC survivors. The clinical significance of this greater distress is unclear, however. While MPC survivors were more likely to have talked to a mental health professional, uptake of mental health care appeared to be suboptimal. MPC and SPC survivors might be considered distinct subgroups and increased attention devoted to potentially unique mental and physical health needs of MPC survivors.