Human parvovirus B19 (B19V) infection in immunocompetent patients usually has a mild clinical course, but during pregnancy it can cause serious and even fatal complications in the fetus. The most common clinical presentation of B19V infection is erythema infectiosum and in this case laboratory confirmation is required for differentiation from other exanthematous diseases. Measles and rubella negative sera collected in Belarus between 2005 and 2008 from 906 patients with a rash and fever were screened for B19V infection by ELISA. More than 35% of the samples (322/906) were positive for B19V. The proportion ranged from 10.1% in 2008 to 53.2% in 2006 when an outbreak took place in Minsk city. All B19V outbreaks and cluster cases occurred during the winter–spring period, but sporadic cases were recorded basically throughout the year. The majority of the cases (56.5%) occurred among the 2 till 10 year old children, and 27.3% of the cases were observed in adults between 19 and 53 years. All 104 B19V strains sequenced in the NS1/VP1u region belonged to genotype 1 with a maximal genetic distance of 1.75%. The two phylogenetic clusters reflected the geographic origins of the viruses within the country. Forty-two unique nucleotide mutations as compared to sequences downloaded from GenBank were found in the VP1u and NS1 regions; most of these changes were nonsynonymous. This report highlights the importance of B19V infection in patients with a rash and fever in Belarus. J. Med. Virol. 84:973–978, 2012. © 2012 Wiley Periodicals, Inc.