Upright microscopes are used in life sciences and cell biology for phase contrast, brightfield, darkfield, differential interference contrast (DIC), polarization, or fluorescence microscopy of slide samples. Upright microscopes can also be used in the microscopy of fixed cells or tissue samples.

In an upright microscope, the light source and condenser are located beneath the stage and, therefore, the specimen. Light is transmitted through the sample from below, and it can then be viewed from above with an ocular lens.

While with an inverted microscope, gravity naturally causes cells to sink to the bottom and adhere to the coverslip, when using an upright microscope for cell biology applications, the samples are instead squeezed between the coverslip and a slide. This allows the sample to be successfully viewed and analyzed with the upright microscope from above.