ANXA1 (Annexin-A1), originally known as an anti-inflammatory mediator, has been implicated in cancer. However, its functions in cancer growth and metastasis are unclear and conflicting. ANXA1 expression may be dependent on the stage or type of cancer. ANXA1 acts as a double-edged sword as it is generally antiproliferative, protecting cells against DNA damage, despite promoting metastasis. The use of ANXA1 as a therapeutic or prognostic marker for cancer must be carefully timed, and it must be employed carefully depending on the cancer type, grade, and stage.