Primary cilia, microtubule-based organelles protruding from the surfaces of most eukaryotic cells, have critical roles in maintaining cellular homeostasis, by sensing, transducing, and transmitting diverse extracellular and intracellular signals through multiple signaling pathways, including the Hedgehog, Notch, and Wnt pathways. Consequently, structural or functional abnormalities in primary cilia often lead to various human diseases, including cancer. Although primary cilia are frequently absent in most cancer types, they paradoxically facilitate tumor initiation and progression in certain malignancies. Therefore, elucidating the complex interplay between primary cilia and cancer might provide novel insights for cancer treatment. In this review, we summarize current insights into the structure and function of primary cilia, explore their roles in key tumor-associated signaling pathways, and discuss emerging evidence linking ciliary dysfunction to cancer development and progression. We also highlight recent advances in targeting cilia-associated mechanisms as potential therapeutic strategies in oncology.