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According to The International Agency for Research on Cancer (IARC) survey, the most commonly diagnosed breast cancer (BC) encumbrance will rise to ˃3 million with ˃1 million bereavements per year by 2040. This creates a high demand for effective early diagnosis of BC to reduce psychological and economic distress. Recently, the body fluid cancer biomarkers detection, a minimally invasive method has an imperative role to identify the cancer stages for developing new strategies for early diagnosis. Traditional complicated and sophisticated detection tool preparation and time consuming detection technologies are lately replaced with nanotechnology incorporated Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein (CRISPR/Cas) technology based biosensors. This technology is an in vitro, next generation ultrasensitive diagnostic device meant to achieve highly specific, ultra-sensitive, and rapid identification of BC nucleic acids, protein biomarkers, whole cells, and small molecules. Till date, many reviews focussing on the use of this technology in diagnosing contagious diseases, liver and colon cancers and later state BC biomarkers are published. Yet review article highlighting the CRISPR/Cas modified biosensors and point-of-care devices (POCDs), exclusively for early BC detection is rarely reported. Hence, this review involves critical thinking on CRISPS-Cas based biosensors research published between Jan 2017–Nov 2022 especially for early BC biomarkers based liquid biopsy diagnosis to develop ultrasensitive and rapid POC tool. The challenges faced by the researchers to bring out CRISPR based biosensing into real time and the future perspectives are also briefed at the end.