BranchSampler is a system for computer-assisted manual stereology written for handheld devices running Windows CE. The system has been designed specifically to streamline data collection and optimize sampling of tree-like branching structures, with particular aims of reducing user errors, saving time, and saving data in formats suited for further analysis in other software, for example, a spreadsheet. The system can be applied in a wide range of applications, from biomedical science to agriculture and horticulture. It can be applied for sampling nested generations of lung bronchioles and renal arterioles or for collection and optimizing sampling of crops for precision agriculture. Although the system has been designed specifically for sampling branching structures, it is sufficiently flexible to be used for other applications involving nested stereological designs. We describe the system specifications, software and Graphical User Interface development, functionality and application of the handheld system using four examples: (a) sampling monkey lung bronchioles for estimation of diameter and wall thickness (b) sampling rat kidney for estimating number of arteries and arterioles in a specific generation (c) mapping fruit (apple) tree yield in an orchard and (d) estimating the total leaf surface area of chrysanthemum plants in a greenhouse.