Principal component analysis (PCA) plays an important role in the analysis of cryo-electron microscopy (cryo-EM) images for various tasks such as classification, denoising, compression, and ab initio modeling. We introduce a fast method for estimating a compressed representation of the 2-D covariance matrix of noisy cryo-EM projection images affected by radial point spread functions that enables fast PCA computation. Our method is based on a new algorithm for expanding images in the Fourier–Bessel basis (the harmonics on the disk), which provides a convenient way to handle the effect of the contrast transfer functions. For $ N $ images of size $ L\times L $ , our method has time complexity $ O\left({NL}^3+{L}^4\right) $ and space complexity $ O\left({NL}^2+{L}^3\right) $ . In contrast to previous work, these complexities are independent of the number of different contrast transfer functions of the images. We demonstrate our approach on synthetic and experimental data and show acceleration by factors of up to two orders of magnitude.