In 1992, the cytokine-like natural killer cell transcript 4 (NK4) was discovered, which was shown to be selectively expressed in lymphocytes (Dahl et al., 1992). The identity of NK4 was not known until 2005 when the protein was reclassified as the inflammatory interleukin, IL-32 (Kim et al., 2005). Since then, IL-32 has been shown to have different effects on various cancers, such as colon cancer, breast cancer, lung cancer, and more. On one hand, IL-32 has been associated with the NF-κB, p38/MAPκ, STAT3, MMP2, MMP9, AKT, and STAT5 pathways which have been shown as having pro-tumor effects. On the other hand, IL-32 has also been associated with the COX-2, p21, p53, and TRAILR pathways which are shown as having anti-tumor effects. The diverse and seemly paradoxical roles of IL-32 in neoplasia are what make it such an interesting topic in the realm of cancer research. To date, IL-32 is known to have nine different isoforms: IL-32α, IL-32β, IL32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and small IL-32. Each reacts differently to the various protein pathways that have been studied and have been shown to be specifically expressed by certain types of cells. For example, the isoform IL-32α has been demonstrated to cause the upregulation of IL-8, TNF, and CCL2 which induces inflammation (Catalán et al., 2017). On the other hand, the isoform IL-32θ has been shown to have anti-inflammatory effects which can act as a tumor suppressor (Khawar et al., 2017). Some cancers have shown a correlation between IL-32 and the severity of the disease which can serve as a marker for the prognosis or could pose some potential therapeutic options (Zhai et al., 2019, Kang and Kim, 2021). Receptors for extracellular signaling have yet to be found for IL-32 (Kim et al., 2005). In this review, we will explore what is currently known about IL-32, including its relationship with tumorigenesis and the potential for IL-32 to enhance local and systemic anti-tumor immune responses.