AbstractA single CRP measurement is insufficient to examine the association of long‐term patterns of CRP concentration with cancer risk. We prospectively examined the relationship between CRP trajectory patterns and new‐onset cancers among 52 276 participants. Latent mixture modeling was used to identify CRP trajectories. Cox proportional hazards regression models were used to evaluate the association between CRP trajectory patterns and the risk of overall and specific‐site cancer. Four CRP trajectories patterns were identified: low‐stable pattern (n = 43 258), moderate‐increasing pattern (n = 2591), increasing‐decreasing pattern (n = 2068) and elevated‐decreasing pattern (n = 4359). Relative to the low‐stable pattern, the moderate‐increasing trajectory pattern was associated with an elevated risk of overall, lung, breast, leukemia, bladder, stomach, colorectal, liver, gallbladder or extrahepatic bile duct cancer and leukemia. Participants in the increasing‐decreasing trajectory pattern were associated with an elevated risk of overall, lung, breast, bladder, pancreatic and liver cancer. The increasing‐decreasing trajectory pattern was also associated with decreased risk of colorectal cancer in the multivariate analyses. Elevated‐decreasing trajectory pattern was associated with increased risk of leukemia and decreased risk of esophageal and colorectal cancer. CRP trajectories play an important role in the occurrence of cancers, especially in the lung, breast, bladder, stomach, colorectal, liver, gallbladder and extrahepatic bile duct cancer and leukemia.