We report on the construction, production, and characterization of a new fully human dimeric immunoRNase, obtained by fusion of Erbicin, a human anti-ErbB2 single-chain antibody fragment (scFv), with a dimeric mutant of human pancreatic RNase (HHP2-RNase). This novel immunoagent with 2 scFv moieties each fused to 1 of the 2 subunits of the dimeric RNase, called ERB-HHP2-RNase, has shown improved biologic properties with respect to the previously reported monomeric ERB-hRNase immunoRNase: it selectively binds ErbB2-positive cancer cells with an increased avidity; it is not inhibited by the cytosolic ribonuclease inhibitor; it is endowed with a more powerful cytotoxic activity.