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The number zero holds a special status among numbers, indispensable for developing a comprehensive number theory. 1,2,3,4 Despite its importance in mathematics, the neuronal foundation of zero in the human brain is unknown. We conducted single-neuron recordings in neurosurgical patients 5,6,7 while they made judgments involving nonsymbolic number representations (dot numerosity), including the empty set, and symbolic numbers (Arabic numerals), including numeral zero. Neurons showed responsiveness to either the empty set or numeral zero, but not both. Neuronal activity to zero in both nonsymbolic and symbolic formats exhibited a numerical distance effect, indicating that zero representations are integrated together with countable numerosities and positive integers at the low end of the number line. 8,9 A boundary in neuronal coding existed between the nonsymbolic empty set and small numerosities, correlating with the relative difficulty in discriminating numerosity zero behaviorally. Conversely, no such boundary was found for symbolic zero activity, suggesting that symbolic representations integrate zero with other numerals along the number line, reconciling its outlier role. The status of zero as a special nonsymbolic numerical quantity is reflected in the activity of neurons in the human brain, which seems to serve as a scaffold for more advanced representations of zero as a symbolic number. • Single-neuron recordings in the medial temporal lobe of patients • Neurons signal both nonsymbolic and symbolic zero • Neuronal representations of zero integrated along the number line • Nonsymbolic empty sets distinctly encoded from other small numbers Kutter et al. identify and characterize single-neuron activity in the human brain correlated with the representation of both nonsymbolic (dot numerosities) and symbolic (Arabic numerals) number zero. [ABSTRACT FROM AUTHOR]