The MALT1 (MALT1 paracaspase, a.k.a. MLT) gene encodes a human paracaspase and is often rearranged in MALT lymphomas accounting for 5-10% of all B-cell non-Hodgkin lymphomas (NHL). The most common translocations affecting the MALT1 gene are t(11;18)(q22.2;q21.3) and t(14;18)(q32.3;q21.3) occurring in 50% and 15-20% of MALT lymphomas, respectively. These translocations lead to the expression of BIRC3-MALT1 (a.k.a. API2- MALT1) and IGH-MALT1 fusion proteins, resulting in constitutive activation of the NF-κB signaling pathway which controls the expression of numerous anti-apoptotic and proliferation-promoting genes. The translocation t(11;18)(q22.2;q21.3) is mainly found in pulmonary and gastric lymphomas, whereas t(14;18) (q32.3;q21.3) occurs more frequently in non-gastrointestinal MALT lymphomas, e.g., of the skin and salivary glands. The presence of a t(11;18)(q22.2;q21.3) correlates with unresponsiveness to eradication of Helicobacter pylori in gastric MALT lymphomas. Hence, detection of MALT1 translocations by Fluorescence in situ Hybridization (FISH) may be a supportive tool to identify patients eligible for anti H. pylori therapy.