Francesca Farina, Alessandra Stasia, Carlo Gambacorti-Passerini Department of Health Sciences, University of Milano Bicocca, Monza, Italy Abstract: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase protein implicated in a variety of hematological malignancies and solid tumors. ALK contributes to the development of cancers in different cell lineages through a variety of genetic mechanisms: gene fusions, activating point mutations, and possibly gene amplification. Recent developments led to significant therapeutic advances, including efficient diagnostic tests and ALK-targeting agents. This review addresses some therapeutic considerations with regard to the use of ALK inhibitors in ALK-positive lymphomas where, in spite of the advanced stage of the disease, long-lasting responses could be obtained in a substantial portion of heavily pretreated patients. Data and mechanisms for the development of resistance to ALK inhibitors will also be presented and discussed. Keywords: ALK, lymphoma, tyrosine kinase, targeted therapy, crizotinib