We considered flavonoids and proanthocyanidins in a network of multicentric Italian case-control studies including about 10,000 incident, histologically confirmed cases of selected cancers and over 16,000 controls. Odds ratios (ORs) for the highest vs. the lowest quintile of 6 classes of flavonoids and proanthocyanidins were estimated by multiple logistic regression models. Total flavonoids, flavanones, and flavonols were inversely related to oral and laryngeal cancers (ORs, respectively 0.56 and 0.60 for total flavonoids; 0.51 and 0.60 for flavanones; and 0.62 and 0.32 for flavonols). Flavanols were also inversely related to laryngeal cancer (OR = 0.64), whereas flavanones were inversely related to esophageal cancer (OR = 0.38). A reduced risk of colorectal cancer was found for high intake of anthocyanidins (OR = 0.67), flavonols (OR = 0.64), flavones (OR = 0.78), and isoflavones (OR = 0.76). Inverse relations with breast cancer were found for flavones (OR = 0.81) and flavonols (OR = 0.80). Flavonols (OR = 0.63) and isoflavones (OR = 0.51) were inversely associated to ovarian cancer, whereas flavonols (OR = 0.69) and flavones (OR = 0.68) were inversely associated to renal cancer. No association between flavonoids and prostate cancer emerged. We found inverse associations between proanthocyanidins and colorectal cancer. These associations appeared stronger for proanthocyanidins with a higher degree of polymerization (OR = 0.69 for ≥ 10 mers).