Precision medicine promises to better classify patients by individual clinical and biological biomarkers, which may provide an accurate assessment of disease risk, diagnosis, prognosis and treatment response. Cancer frequently displays substantial inter-tumor and intra-tumor heterogeneity and hence oncology is well suited for application of precision approaches. Recent studies have demonstrated that dysregulated lncRNAs play pivotal roles in tumor heterogeneity. In this review, attention is focused on the potential applications of lncRNAs as biomarker candidates for cancer risk evaluation, detection, surveillance and prognosis. LncRNAs are often stable in clinical samples and easily detected. The functional implications and therapeutic potential of targeting lncRNAs in human cancer are further discussed. Finally, existing deficiencies and future perspectives in translating fundamental lncRNA knowledge into clinical practice are highlighted.