Developing disposable biosensors with ultrahigh sensitivity, especially with accurately quantitative capability, is challenging but highly desirable for disease intervention prior to the occurrence of severely irreversible symptoms or even death. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. We find that an ultimate sensitivity with over six orders of magnitude enhancement over the saturated monolayer lasers can be achieved by reducing the fluorophores close to the threshold density (~3.2 × 10 −13 mol/cm 2 ). We further achieve an ultrasensitive immunoassay for a Parkinson's disease biomarker, alpha-synuclein, with a lower limit of detection of 0.32 pM in serum. These findings represent a critical step toward using the ultrasensitive optical microcavities in early diagnosis, enabling new opportunities to develop easy use and quantitative biosensors for high-throughput clinical diagnosis with ultimate sensitivity.