Massive evidence has accumulated over the last decades about a positive association between insulin resistance and the risk for colorectal cancer. But is enhanced colonic epithelial proliferation really due to increased plasma insulin levels? The present work tries to give an answer to this question by elucidating the effect of hyperinsulinemia on epithelial proliferation and the underlying signaling mechanisms in a small Austrian study population. The outcomes of this study came as a surprise and have led to new scientific insights.