A group of neoplasms that share the characteristic light microscopic appearance of being composed of relatively small, round to round-spindled, monotonous, seemingly undifferentiated cells. It comprises all significant categories of neoplasms- carcinomas, sarcomas, lymphomas, and neuroendocrine- neuroectodermal tumors. Hence microscopic similarity between them and the diagnosis in routine histologic examination extremely difficult. This heterogeneous group of lesions becomes a diagnostic challenge. The diagnosis depends on clinical, radiological, pathological and genetic features. Each lesion has its own has distinctive features but histopathologically termed as ‘round cell tumors’. This article provides an insight into this group of intriguing round cell lesions, which are characterized by varied histopathological features and their associated confirmatory immuno-histochemical markers for a reliable and a consistent diagnosis.