The majority of the human genome is comprised of non-protein-coding genes, but the relevance of non-coding RNAs in complex diseases has yet to be fully elucidated. One class of non-coding RNAs is long non-coding RNAs or lncRNAs, many of which have been identified to play a range of roles in transcription and translation. While the clinical importance of the majority of lncRNAs have yet to be identified, it is puzzling that a large number of disease-associated genetic variations are seen in lncRNA genes. The 8q24.21 locus is rich in lncRNAs and very few protein-coding genes are located in this region. Interestingly, the 8q24.21 region is also a hot spot for genetic variants associated with an increased risk of cancer. Research focusing on the lncRNAs in this area of the genome has indicated clinical relevance of lncRNAs in different cancers. In this review, we summarise the lncRNAs in the 8q24.21 region with respect to their role in cancer and discuss the potential impact of cancer-associated genetic polymorphisms on the function of lncRNAs in initiation and progression of cancer.