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The translocation t(4; 14)(p16; q32) is one of the most common translocations in multiple myeloma (MM) and is associated with very poor prognosis. The t(4; 14) translocation leads to the simultaneous overexpression of two genes,<jats:italic>FGFR3<\/jats:italic>(fibroblast growth factor receptor 3) and<jats:italic>MMSET<\/jats:italic>(multiple myeloma SET domain), both of which have potential oncogenic activity. However, approximately 30% of t(4; 14)\u2009MM patients do not express FGFR3 and have poor prognosis irrespective of FGFR3 expression, whereas MMSET overexpression is universal in t(4; 14) cases. In this review, we provide an overview of recent findings regarding the oncogenic roles of MMSET in MM and its functions on histone methylation. 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