The recent wide geographic spread of the highly pathogenic avian influenza A/H5N1 virus has important public health implications. Several wild migratory birds were confirmed to be infected with avian influenza A/H5N1 in Greece in February and March 2006. The aim of this paper is to report data from potential H5N1 human cases that presented to local hospitals during this period with a respiratory infection and expressing concern about exposure to avian influenza. A case-control investigation was conducted that included case identification with the use of a structured definition, review of epidemiological and clinical characteristics and molecular testing for avian influenza A/H5N1. The setting was the entire country of Greece during February and March 2006. The main outcomes were rates of possible cases (meeting both a clinical and an epidemiological criterion) and clinical or epidemiological characteristics differentiating them from potential cases that met either one of the criteria of a possible case, but not both. Twenty six potential patients (81% of whom met a clinical criterion, and 39% of whom met an epidemiological criterion) presented and most (85%) were admitted in local hospitals during the period of interest. The majority of cases (85%) were observed in northern Greece where most of the confirmed A/H5N1 avian cases were documented. Five of the 26 evaluated patients met the definition of a possible case. These clustered within the early period of confirmed A/H5N1 cases in wild migratory birds (P=0.05). Molecular testing was negative for all possible cases. Application of a revised case definition constructed according to newer European Union guidance resulted in the exclusion of two possible cases. Several potential A/H5N1 human cases were recently identified in Greece. Both the timing of identification and the geographical location of potential cases suggest an increased awareness on the part of the general public, as well as poor interpretation of the case definition by the clinicians.