Background. Cancer in childhood is rare, but nevertheless one of the most frequent causes of disease related death. Initial symptoms are often unspecific, frequently leading to a delay of cancer diagnosis. As a timely diagnosis can be crucial for the clinical outcome, our aim is to point out when unspecific symptoms should be considered suspect of being associated with specific cancer entities. Data sources. A systematic literature research in PubMed and current biliographies, as well as an evaluation of published epidemiologic data was performed. Results. This article reviews the typical presenting features and epidemiologic characteristics of the more common childhood malignancies, elucidates when specific and virtually unspecific symptoms require further evaluation, and gives advice how to start a rational diagnostic workup. Furthermore, genetic syndromes requiring increased watchfulness for cancer in childhood are demonstrated. Conclusion. Patients showing suspect symptoms should early be referred to specialized centres to assure optimal diagnostic and therapeutic capabilities.