Neithhotep lived at the beginning of the First Dynasty, around 3100 BCE, when writing, royal titulary and the institutions of kingship were still developing. Her name is conventionally written Neithhotep, although the grammar behind the signs can also be read as Hetep-Neith because Egyptian writing often placed a divine name first out of respect. The name invokes Neith, the ancient goddess associated especially with Sais in the Delta. That connection has encouraged theories that Neithhotep came from Lower Egypt and that her marriage helped bind northern and southern elites after unification, but no surviving inscription states such a political marriage directly.

Her most famous monument is the great palace-facade mastaba at Naqada, discovered by Jacques de Morgan in 1897 and once called the Tomb of Menes. The building was exceptional in size and design for its date, and numerous objects from the complex carried the names of early rulers and royal people. Neithhotep's name appears repeatedly among the finds, while sealings of Aha show that the monument was active in his reign. For much of modern Egyptology the tomb was identified as hers, although more recent scholarship has warned that the occupant is not absolutely certain. Even with that caution, the monument and its contents demonstrate the extraordinary wealth and administrative reach of the royal household with which she was associated.

Neithhotep's place within that household is reconstructed from scattered inscriptions rather than from a narrative record. She is often described as the wife of Narmer and mother of Aha, a reconstruction that fits the sequence of names and the dating of objects connected with her. The Metropolitan Museum of Art, for example, preserves a clay jar sealing impressed with her name from the Naqada royal tomb and dates it to the reign of Aha around 3100 BCE. Because the surviving evidence belongs to the same narrow period, Neithhotep stands immediately beside Narmer and Aha in the archaeological record even though no text gives us a conventional royal biography.

Her political role is more difficult to define. Neithhotep's name appears in forms that resemble the display conventions of royal authority, and the scale of the Naqada monument encouraged early scholars to wonder whether she had ruled in her own right. Later researchers have proposed that she may have acted as a regent during the transition between kings, but the evidence does not identify a regency as clearly as the later First Dynasty evidence for Merneith. The safest conclusion is that Neithhotep was a woman of exceptional royal rank whose authority may have extended beyond the normal household roles later assigned to queens. Calling her Egypt's first female pharaoh would go further than the surviving evidence allows.

Her name continued to occur in early royal contexts, including objects from Abydos and material associated with the generations after Aha, although identical or similar personal names need not always refer to the same woman. This is a reminder of how little survives from Egypt's first dynasty: names on jars, tags, sealings and tomb equipment must carry the weight that later periods place on chronicles and monumental inscriptions. Neithhotep therefore matters not because we possess a detailed account of her life, but because the physical record gives a woman a conspicuous place at the foundation of Egyptian kingship. Beside Narmer, Aha and the goddess Neith whose name she bore, she stands at the threshold between Predynastic rule and the dynastic state.