In contemporary biology and medicine, 3D microscopy is one of the most widely-used techniques for imaging and manipulation of various kinds of samples. Navigating such a micrometer-sized, 3-dimensional sample under the microscope -- e.g. to find relevant imaging regions -- can pose a tedious challenge for the experimenter. In this paper, we examine whether 2D desktop, 3D desktop, or Virtual Reality (VR) interfaces provide the best user experience and performance for the exploration of 3D samples. We invited 12 skilled microscope operators to perform two different exploration tasks in 2D, 3D and VR and compared all conditions in terms speed, usability, and completion. Our results show a clear benefit when using VR -- in terms of task efficiency, usability, and user acceptance. Intriguingly, while VR outperformed desktop 2D and 3D in all scenarios, 3D desktop did not outperform 2D desktop.

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