This article proposes a lossy three-dimensional (3-D) image compression method for 3-D secondary ion microscopy (SIMS) image sets that uses a separable nonuniform 3-D wavelet transform. A typical 3-D SIMS measurement produces relatively large amounts of data which has to be reduced for archivation purposes. Although it is possible to compress an image set slice by slice, more efficient compression can be achieved by exploring the correlation between slices. Compared to different two-dimensional (2-D) image compression methods, compression ratios of the 3-D wavelet method are about four times higher at a comparable peak signal-to-noise ratio (PSNR).