When one follows a systematic approach to make a diagnosis of a malignant lesion, it is relatively easy to render a correct cancer diagnosis in most cases during routine daily practice. The first step is to recognize whether or not the specimen contains a lesion and then to determine whether the lesion is neoplastic or non-neoplastic. As a neoplasm is a clonal proliferation, neoplastic conditions are consisted of a single cell type, whereas non-neoplastic conditions consist of multiple different cell types. After determining that a lesion is neoplastic, the next step is to decide whether the neoplasm is of an epithelial origin or mesenchymal origin. The main differences between epithelial tumors and mesenchymal tumors include: (1) The tumor cells in epithelial tumors are oval-round to polygonal, but in mesenchymal tumors, the tumor cells are in general spindle-shaped; (2) Epithelial tumors generally form tumor cell nests, but mesenchymal tumors are arranged diffusely in sheets, without forming tumor cell nests; (3) In epithelial tumors, desmoplastic stroma is well formed in between tumor cell nests, but in mesenchymal tumors there is no desmoplastic stroma; and lastly, (4) feeding vessels open in the stroma in epithelial tumors but open directly between tumor cells in mesenchymal tumors. After this, we can decide whether the tumor is benign or malignant. The differences between benign and malignant tumors include; (1) differentiation, (2) growth rate, (3) growth pattern, and (4) metastasis. A benign tumor is well differentiated, grows slowly, shows expansile growth with encapsulation and does not metastasize. In contrast, a malignant tumor is often poorly differentiated, grows rapidly with many mitoses, shows invasive growth with no capsule and frequently metastasizes. In general, malignant tumors show high cellularity, tumor necrosis and nuclear alterations, which include nuclear enlargement with a high nuclear/cytoplasmic ratio, hyperchromatism, pleomorphism, prominent nucleoli, and frequent mitoses. The final step is to classify the type of tumor based on the cellular differentiation and gross and microscopic growth pattern based on the light microscopic examination of hematoxylin and eosin stained slides. For the correct identification of the tumor, immunostaining, molecular diagnostic tools, or possibly electron microscopic evaluation may be required. After making a diagnosis of malignancy, one should then consider the relevant prognostic factors. The 2 well-known prognostic factors (category I prognostic factors) important in almost all tumors include stage and grade. Therefore, information for regarding stage and grade should be included in the pathology report.