The germinal center T-helper cell has been proposed as the cell of origin for angioimmunoblastic T-cell lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of angioimmunoblastic T-cell lymphoma cases, provided further support for this theory. To determine the specifity of this marker for angioimmunoblastic T-cell lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-cell lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the lymphoma cases were considered peripheral T-cell lymphoma, unspecified, and six were reclassified as angioimmunoblastic T-cell lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 angioimmunoblastic T-cell lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-cell lymphoma, unspecified cases (10%). The two peripheral T-cell lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert lymphoma-like histology. While these cases did not meet all histologic criteria for angioimmunoblastic T-cell lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of angioimmunoblastic T-cell lymphoma. In conclusion, CXCL13 expression is a distinctive feature of angioimmunoblastic T-cell lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-cell lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of angioimmunoblastic T-cell lymphoma.