Aim: To assess whether polyp histology can be predicted on the basis of patient characteristics and endoscopic polyp findings. Methods: 2307 polyps from 1397 colonoscopies in 545 consecutive non-FAP patients were documented at the registry for colorectal polyps at the University Hospital of Zurich, Switzerland, over a 13 year period. Using Chi-square tests, patient age (< versus ≥ 60 years), gender, family history of colon polyps or cancer, presence of anemia, polyp size (<5mm versus 5-10mm versus>10mm), polyp location (left-sided including splenic flexure versusrightsided), and total number of polyps (≤ versus >2) were assessed regarding a correlation with insignificant or significant polyp histology (villous component or severe dysplasia or carcinoma). Predictive values (PV) of these parameters for the polyp histology were calculated. Results: Insignificant polyp histology correlated with patient age < 60 (p=0.004), lack of anemia (p<0.001), polyp size <5mm (p<0.001), right-sided polyp location (p=0.018), and total number of polyps >2 (p<0.001). The latter was caused by the high prevalence of hyperplastic polyps at colonoscopies with >2 polyps (36.9% versus19.5%; p<0.001). Stepwise inclusion of the parameters with the highest PVs (table) demonstrated that the association of a <5mm rightsided polyp in a patient <60 years yielded the highest combined PV (96.8%) for an insignificant polyp. None of these polyps contained a carcinoma. Conversely, neither age ≥60, presence of anemia, polyp size >10mm, leftsided location, nor total number of polyps ≤2 demonstrated a PV >75% for the presence of a significant adenoma. Conclusion: A diminutive (<5mm) right-sided colon polyp in a young patient (<60 years) holds a small (3.2%) risk for significant adenomatous tissue. The costly histopathologic examination of such a polyp may not be required as it will not yield any clinically relevant additional information.