HBV might exploit 2 different mechanisms for causing either indolent (mixed cryoglobulinemia) or highly malignant (DLBCL) B-cell lymphoproliferative disorders. In the case of DLBCL, HBV infection of B cells may enhance overall mutagenesis (possibly through APOBEC enzymes) and alter B-cell–specific signaling pathways (possibly through AID). Among the latter, alterations in the FOXO pathway might result in lymphomagenic tonic B-cell receptor signaling. DLBCL cells do not seem to express stereotyped idiotypes putatively recognizing HBV antigens. Conversely, in mixed cryoglobulinemia, continual antigenic stimulation by HBV may drive the clonal expansion of B cells expressing specific stereotyped idiotypes that regress upon suppression of infection by antiviral therapy. There is no evidence suggesting the possibility of progression from mixed cryoglobulinemia to DLBCL.