Studies regarding the efficacy of intraoperative cytopathology (IOC) of surgical specimens in the pediatric population are almost non-existent, despite their recent popularity in adults. To determine the utility of IOC in children, we examined 58 cases from 54 pediatric patients (neonate to 18 years of age) who had cytologic smears performed in addition to or instead of frozen section (FS) examination during their surgical procedure. Knowing only the patient's age, sex, anatomic site, and any pertinent radiographic or historic data, three pathologists independently reviewed and issued a diagnosis using only the IOC smears. Subsequently, in 28 cases that also had accompanying FS examination, both IOC and FS analysis were interpreted for a composite final diagnosis. Three cases were judged unsatisfactory because of sparse cellularity of smears. Correct classification of the smears as being benign or malignant for each pathologist was 98%, 94%, and 94% using IOC alone and 98%, 94%, and 96% using combined IOC and FS examination. The most frequent anatomic sites were bone (15 cases) and lymph node (14 cases). The most common diagnoses were malignant small round cell tumor (22 cases) and benign lymphoid tissue (10 cases). The records of all 55 cases were reviewed in the second phase of our study. Twenty-seven cases (49%) were found in which IOC diagnoses were rendered without a concurrent FS examination. These were correctly interpreted in 26 of 27 cases (96%) in the determination of a benign versus malignant disease process. The tissue sample measured < or = 2 cm in 15 of 27 cases (56%) in this latter group. Intraoperative cytopathology diagnoses in this group were rendered by various faculty members on call for FS examination and, in some cases, by fifth-year residents with faculty supervision. Without minimizing the degree of difficulty in the interpretation of pediatric IOC, we conclude that it serves as a useful supplement in FS diagnosis and, in some situations (particularly when tissue is limited), can replace histologic FS examination.