Cancer-specific cell surface proteins can be targeted for the delivery of therapeutic agents. However, specific proteins may not always be expressed by a tumor. Wang et al. overcome this challenge by designing sugars to selectively label cancer cells. Small-molecule sugars (azides) can be metabolized by enzymes that are highly expressed in some tumors, including colon and breast cancer cells. Metabolized azides labeled endogenous cell surface proteins in cultured cancer cells and tumor-bearing mice. The azide moiety on the labeled proteins was subsequently recognized by another molecule carrying a drug, which was taken up by the cancer cells. Tumor growth was reduced, and animal survival improved by 86%.