The coordinated motion of a cell is fundamental to many important biological processes such as development, wound healing, and phagocytosis. For eukaryotic cells, such as amoebae or animal cells, the cell motility is based on crawling and involves a complex set of internal biochemical events. A recent study reported very interesting crawling behavior of single cell amoeba: in the absence of an external cue, free amoebae move randomly with a noisy, yet, discernible sequence of ‘run-and-turns’ analogous to the ‘run-and-tumbles’ of swimming bacteria. Interestingly, amoeboid trajectories favor zigzag turns. In other words, the cells bias their crawling by making a turn in the opposite direction to a previous turn. This property enhances the long range directional persistence of the moving trajectories. This study proposes that such a zigzag crawling behavior can be a general property of any crawling cells by demonstrating that 1) microglia, which are the immune cells of the brain, and 2) a simple rule-based model cell, which incorporates the actual biochemistry and mechanics behind cell crawling, both exhibit similar type of crawling behavior. Almost all legged animals walk by alternating their feet. Similarly, all crawling cells appear to move forward by alternating the direction of their movement, even though the regularity and degree of zigzag preference vary from one type to the other.