The perinucleolar compartment (PNC) is a subnuclear body characterized by its location to the periphery of the nucleolus. The PNC is a dynamic structure and is highly enriched in RNA-binding proteins and pol III RNA. The structural stability of the PNC is dependent on continuous pol III transcription and the presence of key proteins. The PNC is associated with malignancy both in vitro and in vivo and its presence positively correlates with metastatic capacity, making it a potential cancer marker. Recent studies also suggest an association between the PNC and a specific DNA locus, and ongoing PNC research continues to focus on determining the structure and function of the PNC to understand its role in cancer. This article summarizes the current understanding of PNC structure and function with an emphasis on the association of PNC and malignancy.