It has previously been reported that about 90% of human colon carcinomas express increased levels of the sialyltransferase which adds sialic acid in alpha 2,6 linkage to galactose residues on N-linked chains of glycoproteins. To ascertain whether colon cancer tissues actually express increased amounts of alpha 2,6-sialylated sugar chains on their glycoconjugates, we screened tissue sections of normal colon, benign and malignant colon tumors with digoxigenin-conjugated Sambucus nigra agglutinin (SNA), a NeuAc alpha 2,6Gal/GalNAc-specific lectin. At the concentration of lectin used, epithelial cells of all the 13 normal colon specimens examined were unreactive; 3 out of 8 benign lesions showed a weak reactivity being the remainder unreactive, while 23 out of 26 carcinomas were positive at a variable degree. Qualitative differences were evident among different carcinoma specimens. In some cases a large number of intensely stained intracytoplasmatic particles was present, thus suggesting that reactivity may be associated with secretions, very likely of mucus droplets. In other specimens there was a more uniform distribution of the staining which suggest that reactivity is associated with cell membrane glycoconjugates. These data indicate that the expression of a2,6-sialylated sugar chains is remarkably increased in the majority of colon cancer specimens examined.