Being involved in an anti-Flaviviridae Project, and because of the role played by benzimidazole derivatives as promising inhibitors of the HCV helicase and RNA polymerase, as well as of the Zn finger transcription factor, we synthesized a new series of 2-arylbenzimidazoles and evaluated them for antiviral activity, as well as for antiproliferative activity. Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae). Compounds 15, 28 and 29 resulted moderately active only against Yellow Fever Virus (a Flavivirus) (range 6-27 μM), whereas none of the title benzimidazoles showed any antiviral activity at concentrations not cytotoxic for the resting cell monolayers. Compounds were also tested for antiproliferative activity against a panel of exponentially growing cell lines derived from human haematological and solid tumors. Several new benzimidazoles turned out active. Among them, compound 27 was the most potent against human haematologic and solid tumor cells and turned out to be as potent as Etoposide and more potent than 6-mercaptopurine (6-MP), used as reference antitumor agents.