Current N ⁶-methyladenosine (m⁶A) mapping methods need large amounts of RNA or are limited to cultured cells. Through optimized sample recovery and signal-to-noise ratio, we developed picogram-scale m⁶A RNA immunoprecipitation and sequencing (picoMeRIP–seq) for studying m⁶A in vivo in single cells and scarce cell types using standard laboratory equipment. We benchmark m⁶A mapping on titrations of poly(A) RNA and embryonic stem cells and in single zebrafish zygotes, mouse oocytes and embryos.