Current practice favors serotesting adolescents with a negative history of chickenpox rather than offering presumptive vaccination. Recent epidemiologic data from Greece indicate that a high proportion of adolescents (21.5%) are susceptible to chickenpox. We assessed the reliability of negative varicella history in relation to type of exposure in 311 children and 283 adolescents. In children with social or unknown exposure to varicella, a negative history had a high negative predictive value (NPV = 73.5), supporting the clinical practice of presumptive vaccination. Conversely, children with a negative history and household exposure had a low NPV (13.8), suggesting that pre-vaccination serologic testing is warranted. In conclusion, based on our local epidemiologic data, presumptive varicella vaccination should be offered to all adolescents with the exception of the subgroup of adolescents with household exposure.